The synthesis, structural characterization and biological evaluation of N-(ferrocenylmethyl amino acid) fluorinated benzene-carboxamide derivatives as potential anticancer agents

作者：Butler William E; Kelly Paula N; Harry Andy G; Tiedt Rachel; White Blanaid; Devery Rosaleen; Kenny Peter T M^*

来源：Applied Organometallic Chemistry, 2013, 27(6): 361-365.

DOI：10.1002/aoc.2994

• ferrocene
• bioorganometallic chemistry
• breast cancer
• MCF-7

A series of N-(ferrocenylmethyl amino acid) fluorinated benzene-carboxamide derivatives and have been synthesized by coupling ferrocenylmethyl amine 3 with various substituted N-(fluorobenzoyl) amino acid derivatives using the standard N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride, 1-hydroxybenzotriazole protocol. The amino acids employed in this study were glycine and L-alanine. All of the compounds were fully characterized using a combination of 1H NMR, 13C NMR, 19F NMR, distortionless enhancement by polarization transfer (DEPT)-135, 1H-1H correlation spectroscopy (COSY) and 1H-13C COSY (heteronuclear multiple-quantum correlation) spectroscopy. The compounds were biologically evaluated on the oestrogen-positive MCF-7 breast cancer cell line. Compounds , , and exhibited cytotoxic effects on the MCF-7 breast cancer cell line. N-(Ferrocenylmethyl-L-alanine)-3,4,5-trifluorobenzene-carboxamide () was the most active compound, with an IC50 value of 2.84 m. Compounds , and had lower IC50 values than that found for the clinically employed anticancer drug cisplatin (IC50=16.3 m against MCF-7). Guanine oxidation studies confirmed that was capable of generating oxidative damage via a reactive oxygen species-mediated mechanism.

• 出版日期2013-6